Structure of PDB 2h7c Chain D Binding Site BS01

Receptor Information

>2h7c Chain D (length=532) Species: 9606 (Homo sapiens)

SSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPLGPLRFTPPQP
AEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLN
IYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQY
RLGIWGFFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGE
SAGGESVSVLVLSPLAKNLFHRAISESGVALTSVLVKKGDVKPLAEQIAI
TAGCKTTTSAVMVHCLRQKTEEELLETTLKMKFLSLDLQGDPRESQPLLG
TVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIPMLMSYPLSEG
QLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDLI
ADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDE
LFSVFGAPFLKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYN
QKEGYLQIGANTQAAQKLKDKEVAFWTNLFAK

Ligand information

• Ligand ID: COA
• InChI: InChI=1S/C21H36N7O16P3S/c1-21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16+,20-/m1/s1
• InChIKey: RGJOEKWQDUBAIZ-IBOSZNHHSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: CC(C)(COP(=O)(O)OP(=O)(O)OCC1C(C(C(O1)n2cnc3c2ncnc3N)O)OP(=O)(O)O)C(C(=O)NCCC(=O)NCCS)O
  CACTVS 3.341: CC(C)(CO[P@@](O)(=O)O[P@](O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O[P](O)(O)=O)n2cnc3c(N)ncnc23)[C@@H](O)C(=O)NCCC(=O)NCCS
  OpenEye OEToolkits 1.5.0: CC(C)(CO[P@](=O)(O)O[P@@](=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)n2cnc3c2ncnc3N)O)OP(=O)(O)O)[C@H](C(=O)NCCC(=O)NCCS)O
  CACTVS 3.341: CC(C)(CO[P](O)(=O)O[P](O)(=O)OC[CH]1O[CH]([CH](O)[CH]1O[P](O)(O)=O)n2cnc3c(N)ncnc23)[CH](O)C(=O)NCCC(=O)NCCS
  ACDLabs 10.04: O=C(NCCS)CCNC(=O)C(O)C(C)(C)COP(=O)(O)OP(=O)(O)OCC3OC(n2cnc1c(ncnc12)N)C(O)C3OP(=O)(O)O
• Formula: C21 H36 N7 O16 P3 S
• Name: COENZYME A
• ChEMBL: CHEMBL1213327
• DrugBank: DB01992
• ZINC: ZINC000008551087
• PDB chain: 2h7c Chain B Residue 2

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2h7c Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1
• Resolution: 2.0 Å
• Binding residue (original residue number in PDB): K4302 S4305 L4306 L4308
• Binding residue (residue number reindexed from 1): K282 S285 L286 L288
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): G4142 G4143 S4221 A4222 E4354 H4468
• Catalytic site (residue number reindexed from 1): G122 G123 S201 A202 E334 H447
• Enzyme Commision number: 3.1.1.1: carboxylesterase.
  3.1.1.13: sterol esterase.
  3.1.1.56: methylumbelliferyl-acetate deacetylase.

Gene Ontology

Molecular Function

• GO:0004771 sterol ester esterase activity
• GO:0047374 methylumbelliferyl-acetate deacetylase activity
• GO:0052689 carboxylic ester hydrolase activity
• GO:0106435 carboxylesterase activity

Biological Process

• GO:0006629 lipid metabolic process
• GO:0006695 cholesterol biosynthetic process
• GO:0008203 cholesterol metabolic process
• GO:0009636 response to toxic substance
• GO:0010875 positive regulation of cholesterol efflux
• GO:0010887 negative regulation of cholesterol storage
• GO:0016042 lipid catabolic process
• GO:0030855 epithelial cell differentiation
• GO:0042632 cholesterol homeostasis
• GO:0043691 reverse cholesterol transport
• GO:0051791 medium-chain fatty acid metabolic process
• GO:0070857 regulation of bile acid biosynthetic process
• GO:0071397 cellular response to cholesterol
• GO:0071404 cellular response to low-density lipoprotein particle stimulus
• GO:0090122 cholesterol ester hydrolysis involved in cholesterol transport
• GO:0090205 positive regulation of cholesterol metabolic process
• GO:0120188 regulation of bile acid secretion

Cellular Component

• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005811 lipid droplet
• GO:0005829 cytosol

External links

• PDB: RCSB:2h7c, PDBe:2h7c, PDBj:2h7c
• PDBsum: 2h7c
• PubMed: 16962139
• UniProt: P23141|EST1_HUMAN Liver carboxylesterase 1 (Gene Name=CES1)